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Cocaine (T3D2927)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (15)XML
Targets (15)
Record Information
Version2.0
Creation Date2009-07-21 20:27:56 UTC
Update Date2014-12-24 20:25:53 UTC
Accession NumberT3D2927
Identification
Common NameCocaine
ClassSmall Molecule
DescriptionAn alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [PubChem]
Compound Type
  • Amine
  • Anesthetic
  • Anesthetic, Local
  • Dopamine Uptake Inhibitor
  • Drug
  • Ester
  • Ether
  • Metabolite
  • Organic Compound
  • Synthetic Compound
  • Vasoconstrictor Agent
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
Synonym
(-)-Cocaine
(−)-cocaine
2-Methyl-3beta-hydroxy-1alphah,5alphah-tropane-2beta-carboxylate benzoate (ester)
Benzoylmethylecgonine
beta-Cocain
Cocain
Cocaina
Cocainum
Kokain
L-Cocain
L-Cocaine
Methyl benzoylecgonine
Methyl [1R-(exo,exo)]-3-(benzoyloxy)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
Neurocaine
[1R-(Exo,exo)]-3-(benzoyloxy)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid, methyl ester
Chemical FormulaC17H21NO4
Average Molecular Mass303.353 g/mol
Monoisotopic Mass303.147 g/mol
CAS Registry Number50-36-2
IUPAC Namemethyl (1R,2R,3S,5S)-3-(benzoyloxy)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
Traditional Namecocaine
SMILES[H][C@@]12CC[C@@]([H])(N1C)[C@@]([H])(C(=O)OC)[C@]([H])(C2)OC(=O)C1=CC=CC=C1
InChI IdentifierInChI=1S/C17H21NO4/c1-18-12-8-9-13(18)15(17(20)21-2)14(10-12)22-16(19)11-6-4-3-5-7-11/h3-7,12-15H,8-10H2,1-2H3/t12-,13+,14-,15+/m0/s1
InChI KeyInChIKey=ZPUCINDJVBIVPJ-LJISPDSOSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as benzoic acid esters. These are ester derivatives of benzoic acid.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzoic acids and derivatives
Direct ParentBenzoic acid esters
Alternative Parents
Substituents
  • Benzoate ester
  • Piperidinecarboxylic acid
  • Tropane alkaloid
  • Benzoyl
  • Dicarboxylic acid or derivatives
  • Piperidine
  • N-alkylpyrrolidine
  • Methyl ester
  • Pyrrolidine
  • Amino acid or derivatives
  • Carboxylic acid ester
  • Tertiary aliphatic amine
  • Tertiary amine
  • Carboxylic acid derivative
  • Azacycle
  • Organoheterocyclic compound
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Amine
  • Carbonyl group
  • Organopnictogen compound
  • Organic oxygen compound
  • Organooxygen compound
  • Organic nitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point98°C
Boiling PointNot Available
Solubility1800 mg/L (at 22°C)
LogP2.3
Predicted Properties
PropertyValueSource
Water Solubility5.03 g/LALOGPS
logP1.97ALOGPS
logP2.28ChemAxon
logS-1.8ALOGPS
pKa (Strongest Basic)8.85ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area55.84 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity81.16 m³·mol⁻¹ChemAxon
Polarizability32.36 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-001i-9200000000-5262d40bbcdec08759ab2017-09-12View Spectrum
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-0udi-0109000000-319d789d066a157a09662017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-001i-9200000000-5262d40bbcdec08759ab2018-05-18View Spectrum
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-0udi-0109000000-319d789d066a157a09662018-05-18View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a5a-9620000000-fd84236e0a4ca8f554562017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0udi-0009000000-a2004e33ce1140fd0ed12017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0f89-0908000000-b5abe87da56f09f21f652017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-001i-0900000000-ee9c7f3b491476f49e982017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-001i-0900000000-2dab4b98f61ec4ba24672017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0fz9-0900000000-b3c61e257fbaf700b52b2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-001i-0900000000-3b1dc1a8c8390bfb6c3e2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0udi-0009000000-0479d3211208134ed1402017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0ue9-0709000000-d19680d406708cbbc59b2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-001i-1900000000-5ac8f8a2719f70332b862017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-001i-3900000000-5ff2f6c28b5db03035be2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-053r-8900000000-e597f9f6f5014d501e622017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a5c-9500000000-0fcf099229f1487190782017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0udi-0009000000-ee11934dd1158606bb842017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0ue9-0609000000-bd90cd1f98ce1845ba6b2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-001i-1900000000-9fc49ca16ab794b8c37d2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-001i-3900000000-cb0b593e7f379f7c6aef2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-053r-8900000000-2a88bad614aed29eac522017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a59-9500000000-c9713abdcf52a45d6ed22017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-001i-0900000000-c18cf276038cf1946f202017-09-14View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0859000000-d8747974615dabc865112016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0ac0-0921000000-20e84a94ac21e65e27c32016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-4900000000-1e0f166133422838c0892016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0319000000-e9a39c150cc22fe3585e2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0umi-4955000000-dea1abe1f68405b6dcd22016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0fi9-3900000000-c6cb0f24abf4c5d1446d2016-08-03View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
Toxicity Profile
Route of ExposureCocaine is absorbed from all sites of application, including mucous membranes and gastrointestinal mucosa. By oral or intra-nasal route, 60 to 80% of cocaine is absorbed.
Mechanism of ToxicityCocaine produces anesthesia by inhibiting excitation of nerve endings or by blocking conduction in peripheral nerves. This is achieved by reversibly binding to and inactivating sodium channels. Sodium influx through these channels is necessary for the depolarization of nerve cell membranes and subsequent propagation of impulses along the course of the nerve. Cocaine is the only local anesthetic with vasoconstrictive properties. This is a result of its blockade of norepinephrine reuptake in the autonomic nervous system. Cocaine binds differentially to the dopamine, serotonin, and norepinephrine transport proteins and directly prevents the re-uptake of dopamine, serotonin, and norepinephrine into pre-synaptic neurons. Its effect on dopamine levels is most responsible for the addictive property of cocaine.
MetabolismHepatic. Cocaine is metabolized to benzoylecgonine and ecgonine methyl ester, which are both excreted in the urine. In the presence of alcohol, a further active metabolite, cocaethylene is formed, and is more toxic then cocaine itself. Half Life: 1 hour
Toxicity ValuesOral mouse LD50 = 96 mg/kg LD50: 95.1 mg/kg (i.p, mouse) (8)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesCocaine (KOE-kane) is a local anesthetic. It is applied to certain areas of the body (for example, the nose, mouth, or throat) to cause loss of feeling. This allows some kinds of examinations or surgery to be done without causing pain. (7)
Minimum Risk LevelNot Available
Health EffectsContinued use produces insomnia, hyperactivity, anxiousness, agitation and malnutrition. Overdoses can be lethal.
SymptomsIntense agitation, convulsions, hypertension, rhythm disturbance, coronary insufficiency, hyperthermia, rhabdomyolysis, and renal impairment.
TreatmentThe specific treatment of acute cocaine poisoning is the intravenous administration of a short-acting barbiturate or diazepam. Artificial respiration may be necessary. It is important to limit absorption of the drug. If entrance of the drug into circulation can be checked, and respiratory exchange maintained, the prognosis is favorable since cocaine is eliminated fairly rapidly. (9)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00907
HMDB IDHMDB15043
PubChem Compound ID446220
ChEMBL IDCHEMBL120901
ChemSpider ID10194104
KEGG IDC01416
UniProt IDNot Available
OMIM ID
ChEBI ID27958
BioCyc IDCPD-9776
CTD IDNot Available
Stitch IDCocaine
PDB IDCOC
ACToR IDNot Available
Wikipedia LinkCocaine
References
Synthesis Reference

Nobuyuki Shigetoh, Hiroshi Nakayama, Jinsei Miyazaki, Tadayasu Mitsumata, “Labelling colors for detecting cocaine or methamphetamine, method of preparing the same and detector for cocaine or methamphetamine.” U.S. Patent US5571727, issued October, 1981.

MSDSLink
General References
  1. Siegel RK, Elsohly MA, Plowman T, Rury PM, Jones RT: Cocaine in herbal tea. JAMA. 1986 Jan 3;255(1):40. [3940302 ]
  2. Volkow ND, Wang GJ, Fischman MW, Foltin R, Fowler JS, Franceschi D, Franceschi M, Logan J, Gatley SJ, Wong C, Ding YS, Hitzemann R, Pappas N: Effects of route of administration on cocaine induced dopamine transporter blockade in the human brain. Life Sci. 2000 Aug 11;67(12):1507-15. [10983846 ]
  3. Dimitrijevic N, Dzitoyeva S, Manev H: An automated assay of the behavioral effects of cocaine injections in adult Drosophila. J Neurosci Methods. 2004 Aug 30;137(2):181-4. [15262059 ]
  4. Uz T, Akhisaroglu M, Ahmed R, Manev H: The pineal gland is critical for circadian Period1 expression in the striatum and for circadian cocaine sensitization in mice. Neuropsychopharmacology. 2003 Dec;28(12):2117-23. [12865893 ]
  5. McClung CA, Sidiropoulou K, Vitaterna M, Takahashi JS, White FJ, Cooper DC, Nestler EJ: Regulation of dopaminergic transmission and cocaine reward by the Clock gene. Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9377-81. Epub 2005 Jun 20. [15967985 ]
  6. Busse GD, Riley AL: Effects of alcohol on cocaine lethality in rats: acute and chronic assessments. Neurotoxicol Teratol. 2003 May-Jun;25(3):361-4. [12757832 ]
  7. Drugs.com [Link]
  8. Erowid: Material Safety Data Sheets/ Psychoactive LD50s [Link]
  9. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

Target Details
1. Sodium-dependent dopamine transporter
General Function:
Monoamine transmembrane transporter activity
Specific Function:
Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:
SLC6A3
Uniprot ID:
Q01959
Molecular Weight:
68494.255 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.272 uMNot AvailableBindingDB 22418
Inhibitory0.371 uMNot AvailableBindingDB 22418
Inhibitory0.743 uMNot AvailableBindingDB 22418
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Wilson JM, Levey AI, Bergeron C, Kalasinsky K, Ang L, Peretti F, Adams VI, Smialek J, Anderson WR, Shannak K, Deck J, Niznik HB, Kish SJ: Striatal dopamine, dopamine transporter, and vesicular monoamine transporter in chronic cocaine users. Ann Neurol. 1996 Sep;40(3):428-39. [8797532 ]
  4. Kim DI, Schweri MM, Deutsch HM: Synthesis and pharmacology of site specific cocaine abuse treatment agents: 8-substituted isotropane (3-azabicyclo[3.2.1]octane) dopamine uptake inhibitors. J Med Chem. 2003 Apr 10;46(8):1456-64. [12672245 ]
  5. Rothman RB, Baumann MH, Dersch CM, Appel J, Houghten RA: Discovery of novel peptidic dopamine transporter ligands by screening a positional scanning combinatorial hexapeptide library. Synapse. 1999 Sep 1;33(3):239-46. [10420171 ]
  6. Gong PK, Blough BE, Brieaddy LE, Huang X, Kuhar MJ, Navarro HA, Carroll FI: Synthesis, monoamine transporter binding, properties, and functional monoamine uptake activity of 3beta-[4-methylphenyl and 4-chlorophenyl]-2 beta-[5-(substituted phenyl)thiazol-2-yl]tropanes. J Med Chem. 2007 Jul 26;50(15):3686-95. Epub 2007 Jun 30. [17602602 ]
  7. Cashman JR, Voelker T, Zhang HT, O'Donnell JM: Dual inhibitors of phosphodiesterase-4 and serotonin reuptake. J Med Chem. 2009 Mar 26;52(6):1530-9. doi: 10.1021/jm8010993. [19256502 ]
  8. Pristupa ZB, Wilson JM, Hoffman BJ, Kish SJ, Niznik HB: Pharmacological heterogeneity of the cloned and native human dopamine transporter: disassociation of [3H]WIN 35,428 and [3H]GBR 12,935 binding. Mol Pharmacol. 1994 Jan;45(1):125-35. [8302271 ]
  9. Logan J, Volkow ND, Fowler JS, Wang GJ, Fischman MW, Foltin RW, Abumrad NN, Vitkun S, Gatley SJ, Pappas N, Hitzemann R, Shea CE: Concentration and occupancy of dopamine transporters in cocaine abusers with [11C]cocaine and PET. Synapse. 1997 Dec;27(4):347-56. [9372557 ]
Target Details
2. Sodium-dependent serotonin transporter
General Function:
Serotonin:sodium symporter activity
Specific Function:
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
Gene Name:
SLC6A4
Uniprot ID:
P31645
Molecular Weight:
70324.165 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.276 uMNot AvailableBindingDB 22418
Inhibitory0.601 uMNot AvailableBindingDB 22418
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Patkar AA, Berrettini WH, Hoehe M, Thornton CC, Gottheil E, Hill K, Weinstein SP: Serotonin transporter polymorphisms and measures of impulsivity, aggression, and sensation seeking among African-American cocaine-dependent individuals. Psychiatry Res. 2002 Jun 1;110(2):103-15. [12057823 ]
  4. Barker EL, Moore KR, Rakhshan F, Blakely RD: Transmembrane domain I contributes to the permeation pathway for serotonin and ions in the serotonin transporter. J Neurosci. 1999 Jun 15;19(12):4705-17. [10366604 ]
  5. Corey JL, Quick MW, Davidson N, Lester HA, Guastella J: A cocaine-sensitive Drosophila serotonin transporter: cloning, expression, and electrophysiological characterization. Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):1188-92. [8302852 ]
  6. Cashman JR, Voelker T, Zhang HT, O'Donnell JM: Dual inhibitors of phosphodiesterase-4 and serotonin reuptake. J Med Chem. 2009 Mar 26;52(6):1530-9. doi: 10.1021/jm8010993. [19256502 ]
  7. Gong PK, Blough BE, Brieaddy LE, Huang X, Kuhar MJ, Navarro HA, Carroll FI: Synthesis, monoamine transporter binding, properties, and functional monoamine uptake activity of 3beta-[4-methylphenyl and 4-chlorophenyl]-2 beta-[5-(substituted phenyl)thiazol-2-yl]tropanes. J Med Chem. 2007 Jul 26;50(15):3686-95. Epub 2007 Jun 30. [17602602 ]
  8. Henry LK, Field JR, Adkins EM, Parnas ML, Vaughan RA, Zou MF, Newman AH, Blakely RD: Tyr-95 and Ile-172 in transmembrane segments 1 and 3 of human serotonin transporters interact to establish high affinity recognition of antidepressants. J Biol Chem. 2006 Jan 27;281(4):2012-23. Epub 2005 Nov 3. [16272152 ]
Target Details
3. Sodium-dependent noradrenaline transporter
General Function:
Norepinephrine:sodium symporter activity
Specific Function:
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:
SLC6A2
Uniprot ID:
P23975
Molecular Weight:
69331.42 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.83 uMNot AvailableBindingDB 22418
Inhibitory1.115 uMNot AvailableBindingDB 22418
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Galli A, DeFelice LJ, Duke BJ, Moore KR, Blakely RD: Sodium-dependent norepinephrine-induced currents in norepinephrine-transporter-transfected HEK-293 cells blocked by cocaine and antidepressants. J Exp Biol. 1995 Oct;198(Pt 10):2197-212. [7500004 ]
  4. Burchett SA, Bannon MJ: Serotonin, dopamine and norepinephrine transporter mRNAs: heterogeneity of distribution and response to 'binge' cocaine administration. Brain Res Mol Brain Res. 1997 Oct 3;49(1-2):95-102. [9387868 ]
  5. Zhao Y, Sun L: Perinatal cocaine exposure reduces myocardial norepinephrine transporter function in the neonatal rat. Neurotoxicol Teratol. 2004 May-Jun;26(3):443-50. [15113605 ]
  6. Gong PK, Blough BE, Brieaddy LE, Huang X, Kuhar MJ, Navarro HA, Carroll FI: Synthesis, monoamine transporter binding, properties, and functional monoamine uptake activity of 3beta-[4-methylphenyl and 4-chlorophenyl]-2 beta-[5-(substituted phenyl)thiazol-2-yl]tropanes. J Med Chem. 2007 Jul 26;50(15):3686-95. Epub 2007 Jun 30. [17602602 ]
  7. Cashman JR, Voelker T, Zhang HT, O'Donnell JM: Dual inhibitors of phosphodiesterase-4 and serotonin reuptake. J Med Chem. 2009 Mar 26;52(6):1530-9. doi: 10.1021/jm8010993. [19256502 ]
Target Details
4. D(3) dopamine receptor
General Function:
G-protein coupled amine receptor activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation.
Gene Name:
DRD3
Uniprot ID:
P35462
Molecular Weight:
44224.335 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Ballon N, Leroy S, Roy C, Bourdel MC, Olie JP, Charles-Nicolas A, Krebs MO, Poirier MF: Polymorphisms TaqI A of the DRD2, BalI of the DRD3, exon III repeat of the DRD4, and 3' UTR VNTR of the DAT: association with childhood ADHD in male African-Caribbean cocaine dependents? Am J Med Genet B Neuropsychiatr Genet. 2007 Dec 5;144B(8):1034-41. [17671965 ]
  4. Freimer M, Kranzler H, Satel S, Lacobelle J, Skipsey K, Charney D, Gelernter J: No association between D3 dopamine receptor (DRD3) alleles and cocaine dependence. Addict Biol. 1996;1(3):281-7. [12893467 ]
  5. Le Foll B, Diaz J, Sokoloff P: A single cocaine exposure increases BDNF and D3 receptor expression: implications for drug-conditioning. Neuroreport. 2005 Feb 8;16(2):175-8. [15671872 ]
Target Details
5. Kappa-type opioid receptor
General Function:
Opioid receptor activity
Specific Function:
G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain. Plays a role in mediating reduced physical activity upon treatment with synthetic opioids. Plays a role in the regulation of salivation in response to synthetic opioids. May play a role in arousal and regulation of autonomic and neuroendocrine functions.
Gene Name:
OPRK1
Uniprot ID:
P41145
Molecular Weight:
42644.665 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Chefer VI, Czyzyk T, Bolan EA, Moron J, Pintar JE, Shippenberg TS: Endogenous kappa-opioid receptor systems regulate mesoaccumbal dopamine dynamics and vulnerability to cocaine. J Neurosci. 2005 May 18;25(20):5029-37. [15901784 ]
  4. Yuferov V, Fussell D, LaForge KS, Nielsen DA, Gordon D, Ho A, Leal SM, Ott J, Kreek MJ: Redefinition of the human kappa opioid receptor gene (OPRK1) structure and association of haplotypes with opiate addiction. Pharmacogenetics. 2004 Dec;14(12):793-804. [15608558 ]
  5. Xuei X, Dick D, Flury-Wetherill L, Tian HJ, Agrawal A, Bierut L, Goate A, Bucholz K, Schuckit M, Nurnberger J Jr, Tischfield J, Kuperman S, Porjesz B, Begleiter H, Foroud T, Edenberg HJ: Association of the kappa-opioid system with alcohol dependence. Mol Psychiatry. 2006 Nov;11(11):1016-24. Epub 2006 Aug 22. [16924269 ]
Target Details
6. D(1A) dopamine receptor
General Function:
G-protein coupled amine receptor activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name:
DRD1
Uniprot ID:
P21728
Molecular Weight:
49292.765 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>10 uMNot AvailableBindingDB 22418
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Lee KW, Kim Y, Kim AM, Helmin K, Nairn AC, Greengard P: Cocaine-induced dendritic spine formation in D1 and D2 dopamine receptor-containing medium spiny neurons in nucleus accumbens. Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3399-404. Epub 2006 Feb 21. [16492766 ]
  4. Toll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, Schwartz RW, Haggart D, O'Brien A, White A, Kennedy JM, Craymer K, Farrington L, Auh JS: Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications. NIDA Res Monogr. 1998 Mar;178:440-66. [9686407 ]
Target Details
7. Sodium channel protein type 5 subunit alpha
General Function:
Voltage-gated sodium channel activity involved in sa node cell action potential
Specific Function:
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels.
Gene Name:
SCN5A
Uniprot ID:
Q14524
Molecular Weight:
226937.475 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Antzelevitch C: Brugada syndrome. Pacing Clin Electrophysiol. 2006 Oct;29(10):1130-59. [17038146 ]
  4. Satish OS, Yeh KH, Wen MS: Brugada syndrome--an update. Chang Gung Med J. 2005 Feb;28(2):69-76. [15880981 ]
Target Details
8. Muscarinic acetylcholine receptor M2
General Function:
G-protein coupled acetylcholine receptor activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol.
Gene Name:
CHRM2
Uniprot ID:
P08172
Molecular Weight:
51714.605 Da
References
  1. Carrera MR, Meijler MM, Janda KD: Cocaine pharmacology and current pharmacotherapies for its abuse. Bioorg Med Chem. 2004 Oct 1;12(19):5019-30. [15351386 ]
  2. Sharkey J, Ritz MC, Schenden JA, Hanson RC, Kuhar MJ: Cocaine inhibits muscarinic cholinergic receptors in heart and brain. J Pharmacol Exp Ther. 1988 Sep;246(3):1048-52. [3047364 ]
Target Details
9. Sodium channel protein type 10 subunit alpha
General Function:
Voltage-gated sodium channel activity
Specific Function:
Tetrodotoxin-resistant channel that mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient. Plays a role in neuropathic pain mechanisms.
Gene Name:
SCN10A
Uniprot ID:
Q9Y5Y9
Molecular Weight:
220623.605 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
10. Sodium channel protein type 11 subunit alpha
General Function:
Voltage-gated sodium channel activity
Specific Function:
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant sodium channel isoform. Also involved, with the contribution of the receptor tyrosine kinase NTRK2, in rapid BDNF-evoked neuronal depolarization.
Gene Name:
SCN11A
Uniprot ID:
Q9UI33
Molecular Weight:
204919.66 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
11. Sodium- and chloride-dependent GABA transporter 1
General Function:
Neurotransmitter:sodium symporter activity
Specific Function:
Terminates the action of GABA by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:
SLC6A1
Uniprot ID:
P30531
Molecular Weight:
67073.0 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
12. 5-hydroxytryptamine receptor 1A
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli.
Gene Name:
HTR1A
Uniprot ID:
P08908
Molecular Weight:
46106.335 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>10 uMNot AvailableBindingDB 22418
References
  1. Toll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, Schwartz RW, Haggart D, O'Brien A, White A, Kennedy JM, Craymer K, Farrington L, Auh JS: Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications. NIDA Res Monogr. 1998 Mar;178:440-66. [9686407 ]
Target Details
13. Metallothionein-2
General Function:
Zinc ion binding
Specific Function:
Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids.
Gene Name:
MT2A
Uniprot ID:
P02795
Molecular Weight:
6042.05 Da
References
  1. Brzezinski MR, Spink BJ, Dean RA, Berkman CE, Cashman JR, Bosron WF: Human liver carboxylesterase hCE-1: binding specificity for cocaine, heroin, and their metabolites and analogs. Drug Metab Dispos. 1997 Sep;25(9):1089-96. [9311626 ]
Target Details
14. Muscarinic acetylcholine receptor M1
General Function:
Phosphatidylinositol phospholipase c activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM1
Uniprot ID:
P11229
Molecular Weight:
51420.375 Da
References
  1. Carrera MR, Meijler MM, Janda KD: Cocaine pharmacology and current pharmacotherapies for its abuse. Bioorg Med Chem. 2004 Oct 1;12(19):5019-30. [15351386 ]
Target Details
15. Sigma non-opioid intracellular receptor 1
General Function:
Opioid receptor activity
Specific Function:
Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane. Involved in the regulation of different receptors it plays a role in BDNF signaling and EGF signaling. Also regulates ion channels like the potassium channel and could modulate neurotransmitter release. Plays a role in calcium signaling through modulation together with ANK2 of the ITP3R-dependent calcium efflux at the endoplasmic reticulum. Plays a role in several other cell functions including proliferation, survival and death. Originally identified for its ability to bind various psychoactive drugs it is involved in learning processes, memory and mood alteration (PubMed:16472803, PubMed:9341151). Necessary for proper mitochondrial axonal transport in motor neurons, in particular the retrograde movement of mitochondria (By similarity).
Gene Name:
SIGMAR1
Uniprot ID:
Q99720
Molecular Weight:
25127.52 Da
References
  1. Navarro G, Moreno E, Aymerich M, Marcellino D, McCormick PJ, Mallol J, Cortes A, Casado V, Canela EI, Ortiz J, Fuxe K, Lluis C, Ferre S, Franco R: Direct involvement of sigma-1 receptors in the dopamine D1 receptor-mediated effects of cocaine. Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18676-81. doi: 10.1073/pnas.1008911107. Epub 2010 Oct 18. [20956312 ]